Heroin Use Disorder Research Articles

Regulation of histone acetylation by garcinol blocks the reconsolidation of heroin-associated memory

Drug-associated long-term memories underlie substance use disorders, including heroin use disorder (HUD), which are difficult to eliminate through existing therapies. Addictive memories may become unstable when reexposed to drug-related cues and need to be stabilized again through protein resynthesis. Studies have shown the involvement of histone acetylation in the formation and reconsolidation of long-term drug-associated memory. However, it remains unknown whether and how histone acetyltransferases (HAT), the essential regulators of histone acetylation, contribute to the reconsolidation of heroin-associated memories. Herein, we investigated the function of HAT in the reconsolidation concerning heroin-conditioned memory by using a rat self-administration model. Systemic administration of the HAT inhibitor garcinol inhibited cue and heroin-priming induced reinstatement of heroin seeking, indicating the treatment potential of garcinol for relapse prevention.

Insula Connectivity Abnormalities Predict Impulsivity in Chronic Heroin Use Disorder: A Cross-Sectional Resting-State fMRI Study.

Patients with heroin use disorder (HUD) often exhibit trait impulsivity, which may be an important factor in and a good predictor of addiction. However, the factor structure of HUD trait impulsivity (motor, attentional, and nonplanning) and its neural correlates are not yet known. A total of 24 male volunteers with HUD and 16 healthy control volunteers were recruited for this cross-sectional study. The Barratt Impulsiveness Scale (BIS-11) and resting-state functional magnetic resonance imaging (rs-fMRI) were employed using the insula as a seed point in an effort to understand the association between trait impulsivity and its intrinsic factors and functional connectivity (FC) between the insula and the whole brain. The HUD group in this study exhibited higher total trait impulsivity scores, motor impulsivity, and nonplanning impulsivity than the control group. Changes in FC between the right insula and the lateral occipital cortex and the right angular gyrus were significantly positively correlated with total trait impulsivity scores, motor impulsivity, and nonplanning impulsivity, whereas changes in the FC between the left insula and the left superior frontal gyrus and left frontopolar brain region were significantly negatively correlated with trait impulsivity. Thus, the insula may serve as an important biomarker for identifying trait impulsivity and its intrinsic factor structure in patients with HUDs.

Methadone maintenance treatment is more effective than compulsory detoxification in addressing gut microbiota dysbiosis caused by heroin abuse.

Heroin use disorder (HUD) is commonly accompanied by gut dysbiosis, but the roles of gut microbiota in HUD treatment, such as compulsory detoxification and methadone maintenance treatment (MMT), remain poorly understood. In this study, we performed 16 s rDNA and whole metagenome sequencing to analyze the gut microbial profiles of HUD patients undergoing heroin addiction, heroin withdrawal (compulsory detoxification), and MMT. Our findings revealed that, compared to healthy controls, microbial diversity was significantly decreased in HUD patients who were in a state of heroin addiction and withdrawal, but not in those receiving MMT. We observed significant alterations in 10 bacterial phyla and 20 bacterial families in HUD patients, while MMT partially restored these changes. Whole metagenome sequencing indicated gut microbiota functions were significantly disrupted in HUD patients experiencing heroin addiction and withdrawal, but MMT was found to almost reverse these dysfunctions. In addition, we identified 24 featured bacteria at the genus level that could be used to effectively distinguish between healthy individuals and those with heroin addiction, heroin withdrawal, or receiving MMT. Furthermore, we found the relative abundance of Actinomyces, Turicibacter and Weissella were positively associated with the Hamilton Depression Scale score in different states of HUD patients. This study provides evidence from the gut microbiota perspective that MMT is a more effective approach than compulsory detoxification for HUD treatment.

Methadone maintenance treatment alters couplings of default mode and salience networks in individuals with heroin use disorder: A longitudinal self-controlled resting-state fMRI study.

Methadone maintenance treatment (MMT) is a common treatment for heroin use disorder (HUD). Although individuals with HUD have been reported to show impaired coupling among the salience network (SN), executive control network (ECN), and default mode network (DMN), the effects of MMT on the coupling among three large-scale networks in individuals with HUD remains unclear. Thirty-seven individuals with HUD undergoing MMT and 57 healthy controls were recruited. The longitudinal one-year follow-up study aimed to evaluate the effects of methadone on anxiety, depression, withdrawal symptoms and craving and number of relapse, and brain function (SN, DMN and bilateral ECN) in relation to heroin dependence. The changes in psychological characteristics and the coupling among large-scale networks after 1 year of MMT were analyzed. The associations between the changes in coupling among large-scale networks and psychological characteristics and the methadone dose were also examined. After 1 year of MMT, individuals with HUD showed a reduction in the withdrawal symptom score. The number of relapses was negatively correlated with the methadone dose over 1 year. The functional connectivity between the medial prefrontal cortex (mPFC) and the left middle temporal gyrus (MTG; both key nodes of the DMN) was increased, and the connectivities between the mPFC and the anterior insular and middle frontal gyrus (key nodes of the SN) were also increased. The mPFC-left MTG connectivity was negatively correlated with the withdrawal symptom score. Long-term MMT enhanced the connectivity within the DMN which might be related to reduced withdrawal symptoms, and that between the DMN and SN which might be related to increase in salience values of heroin cues in individuals with HUD. Long-term MMT may be a double-edged sword in treatment for HUD.

Characteristics of Stress Sensitivity in Heroin Use Disorder Patients during Their Opioid Agonist Treatment.

In the present study, performed on a sample of Heroin Use Disorder (HUD) patients undergoing Opioid Agonist Treatment (OAT), we attempted to explore the relationships between stress sensitivity and heroin addiction-related clinical aspects. HUD patients' stress sensitivity was evaluated with the Heroin/PTSD-Spectrum questionnaire (H/PSTD-S). The Drug Addiction History Questionnaire (DAH-Q), the Symptomatological Check List-90 (SCL-90), and The Behavioural Covariate of Heroin Craving inventory (CRAV-HERO) were all used, as were the Deltito Subjective Wellness Scale (D-SWS), a self-report scale evaluating subjective well-being; the Cocaine Problem Severity Index (CPSI), a questionnaire determining the extent of a cocaine problem; and the Marijuana Craving Questionnaire (MC-Q), an instrument assessing craving for cannabinoids. We checked correlations between stress sensitivity and the extent of HUD clinical features and compared patients with and without problematic stress sensitivity. H/PTSD-S was positively correlated with patients' income, altered mental status, legal problems, the lifetime different treatments index, the current treatment load index, and all SCL-90 indexes and factors. Regarding subjective well-being, stress sensitivity negatively correlated with the contrast best week (last five years) index. Patients with high-stress sensitivity were females with a low income. They exhibited a more severe mental status at treatment entry, greater difficulty in working adaptation, and legal problems during treatment. Additionally, these patients showed a higher level of psychopathology, more impairment in well-being, and more risky behaviours during treatment. Stress sensitivity, as H/PTSD-S, must be considered an outcome of HUD. HUD's addiction history and clinical features are significant risk factors for H/PTSD-S. Therefore, social and behavioural impairment in HUD patients could be considered the clinical expression of the H/PTSD spectrum. In summary, the long-term outcome of HUD is not represented by drug-taking behaviours. Rather, the inability to cope with the contingent environmental conditions is the key feature of such a disorder. H/PTSD-S, therefore, should be seen as a syndrome caused by an acquired inability (increased salience) concerning regular (daily) life events.

Differences in small-world networks between methamphetamine and heroin use disorder patients and their relationship with psychiatric symptoms.

Both methamphetamine use disorder (MAUD) and heroin use disorder (HUD) implicated in substance-induced psychosis, but the psychiatirc symptoms induced by MAUD and HUD are significantly different. The functional network organizations that may underlie these differences remains unknown. Image data was acquired by resting-state fMRI from 19 MAUD patients, 21 HUD patients, and 20 healthy controls. The small-world properties, node attributes, and functional connectivity of brain regions were analyzed among the three groups. Psychiatric status was evaluated by the Symptom Checklist 90 in all participants. The MAUD patients had significantly higher psychiatric scores than the controls and HUD patients. Both MAUD and HUD patients still had economical small-world properties. The MAUD patients showed increased nodal efficiency and betweenness centrality in the right inferior occipital gyrus, left insular lobe, bilateral Heschl gyrus, and bilateral superior temporal gyrus, while the node attributes decreased in the right parahippocampal gyrus and right hippocampus compared to the HUD patients. The MAUD patients also showed reduced edge connectivity between left dorsolateral prefrontal cortex (dlPFC) and left middle occipital gyrus (MOG), as well as between bilateral orbitofrontal cortex (OFC) and bilateral superior occipital gyrus (SOG), left MOG, or right cuneus. In the MAUD group, the functional connection between left dlPFC and left MOG was negatively correlated with depression, while the connection between right cuneus lobe and right OFC was negatively correlated with depression and interpersonal sensitivity. These brain regions related to cognitive, emotional, and auditory/visual regulation may play an important role in the psychiatric symptoms of MAUD.

Differences in orexin-A level in the functional brain network of HUD patients undergoing harm reduction therapy.

Orexins regulate the reward-seeking pathway and also play a role in drug addiction. The aim of this study was an investigation of the changes in serum level of orexin-A as well as changes in the functional brain network in heroin use disorder (HUD) patients undergoing harm reduction therapy (HRT).Twenty-five HUD patients undergoing HRT that included methadone and buprenorphine, and 31 healthy control (HC) subjects, were enrolled for this study. Serum orexin-A levels and brain-derived neurotrophic factor were measured with assay kits. The functional brain network in HUD patients and HC was investigated and assessed using seed-based analysis and functional brain MRI scans.t Tested orexin-A levels were found to be significantly higher in HUD patients undergoing HRT than in HCs (P < .05). Analysis showed the functional activity of the right ventral anterior insula (RVAI) in HUD patients to be significantly lower than in HCs (P < .05, Family-Wise Error) corrected). In addition, the internetwork functional connectivity was significantly lower in the left nucleus accumbens and left dorsal anterior insula in the HUD subjects than in HCs (P < .05, Family-Wise Error corrected).In this study, no significant correlation between orexin-A levels and functional brain networks was found. However, the results suggest that HRT might increase orexin-A levels and decrease functional activity in RVAI in HUD patients.

Abnormal brain oscillations and activation of patients with heroin use disorder during emotion regulation: The role of delta- and theta-band power

BackgroundEmotion dysregulation is a crucial component of substance use disorders in predisposition, maintenance, and relapse. Emotional regulation strategies are an important factor in emotion dysregulation. However, studies on heroin use disorder (HUD) patients' ability to use emotion regulation strategies are scarce. MethodsTime-frequency-based analyses were used to compare the power of 33 patients with HUD and 28 healthy controls to elucidate whether patients with HUD have abnormal neural oscillations during passive viewing and emotion regulation strategies. Using the standardized low-resolution brain electromagnetic tomography algorithm (sLORETA), we estimated the possible sources of the anomalous band power. ResultsCompared to patients with HUD, healthy controls showed a stronger decrease in the power of the delta/theta band across all task conditions. The effect peaked at approximately 1300–1900 ms after stimulus onset and varied by task condition. The estimation of sLORETA suggested the frontal, parietal, and limbic lobes as possible generators. LimitationsWe cannot exclude the potential influence of additional factors, such as sex, depression and anxiety levels, and polysubstance use, on the results. ConclusionsPatients with HUD have blunted arousal and impaired ability to use emotion regulation strategies. The abnormal patterns described above may be the underlying neurophysiological basis for this dysfunction. Future studies could combine different approaches to improve emotion dysregulation in patients with HUD to promote treatment outcomes.

Influence of improved behavioral inhibition on decreased cue-induced craving in heroin use disorder: A preliminary intermittent theta burst stimulation study

BackgroundImpaired behavioral inhibition is a critical factor in drug addiction and relapse. Repetitive transcranial magnetic stimulation (rTMS) reduces the craving of heroin-addicted individuals for drug-related cues. However, it is unclear whether this technique also improves impaired behavioral inhibition and how improved behavioral inhibition affects craving. ObjectiveThe intermittent theta-burst stimulation (iTBS) has been recently shown to be non-inferior relative to rTMS for depression. Here, we aim to investigate the effect of iTBS on heroin-addicted individuals' behavioral inhibition and cue-induced craving and the relationship between the alteration of behavioral inhibition and craving. Method42 of 56 initially recruited individuals with the heroin-use disorder in the abstinent-course treatment were randomized to undergo active or sham iTBS to the left dorsolateral prefrontal cortex and received three daily iTBS treatments for 10 consecutive days. We measured participants' performance during a two-choice oddball task (80% standard and 20% deviant trials) and heroin-related cue-induced craving before and immediately after treatment. ResultsThe group that received active iTBS showed significantly improved two-choice oddball task performance after 10 days of intervention compared to both pre-intervention and the group who received sham iTBS. Similarly, a significant reduction in cue-induced craving was observed after following the intervention in the active iTBS group but not the sham iTBS group. The moderation model indicated that iTBS categories play a significant moderating role in the relationship between accuracy cost changing and altered cue-induced craving. ConclusionsThe iTBS treatment protocol positively affects behavioral inhibition in patients with heroin addiction. Improvements in behavioral inhibition can substantially reduce craving.

P34. Substance Use Disorder Treatment Reduces Drug-Biased Reactivity in Heroin Use Disorder Suggested by Preliminary Results – an fMRI Study

Enhanced cortico-striatal reactivity to drug-cues coupled with blunted reactivity to non-drug-reinforcers is a core characteristic of drug addiction. Cognitive reappraisal of drug-cues and savoring of non-drug-reinforcers have decreased drug cue-reactivity; however, the neural mechanisms mediating these effects in heroin use disorder (HUD), and potential changes via abstinence during treatment, remain unresolved.

Difference in topological organization of white matter structural connectome between methamphetamine and heroin use disorder

The psychological symptoms caused by heroin and methamphetamine are significantly different in people with substance use disorders. The topological organization of structural connections that may underlie these differences remains unknown. The study sample consisted of 23 males with methamphetamine use disorder (MAUD), 20 males with heroin use disorder (HUD), and 21 male healthy controls (HCs) who were demographically matched. Diffusion tensor imaging and probabilistic tractography were used for white matter network construction. Psychological symptoms were evaluated by the Symptom Checklist-90. Using graph theoretical analysis, we examined the difference in graph-level and nodal-level properties among the groups. The network Hubs distribution and the relationship between the network alterations and psychological symptoms were identified. The MAUD group demonstrated significantly higher scores on anxiety, hostility, and symptoms of schizophrenia than the HUD and HCs groups. The HUD group showed significantly higher global efficiency and network strength than the HCs group, and higher network strength than the MAUD group. Compared with the HUD group, the MAUD group showed significantly lower Nodal Strength and efficiency, distributed mainly in the temporal, parietal, and occipital regions. We also found the network Hubs were decreased in the MAUD group, but increased in the HUD group. The Nodal Strength in the right superior temporal gyrus was significantly correlated with psychological symptoms in the MAUD group. These findings reflect the significant differences in topological structural connection between HUD and MAUD. This evidence helps shed some light on the neurobiological mechanisms of the psychological differences between HUD and MAUD, and extend our understanding of the structural disruption underlying MAUD-related psychological symptoms.

The Association of Drug-Use Characteristics and Active Coping Styles With Positive Affect in Patients With Heroin-Use Disorder and Methamphetamine-Use Disorder During the COVID-19 Pandemic

Background: Positive affect (PA) is crucial for individuals to cope with the current pandemic and buffer the lingering fears after it, especially for patients with substance-use disorders (SUDs). The current study aimed to explore PA and its related factors during the COVID-19 pandemic in male patients with the heroin-use disorder (HUD) and patients with the methamphetamine-use disorder (MAUD), respectively.Methods: A total of 325 male patients with SUDs (106 with HUD and 219 with MAUD, all were single-substance users) in a compulsory rehabilitation center underwent semi-structured interviews during the pandemic. The demographic information, drug-use characteristics, active coping styles (ACSs, by Simple Coping Style Questionnaire), and PA (by the Positive and Negative Affect Scale) of participants were collected and recorded.Results: There were significant differences between the two groups in age, the proportion of full-time workers before the epidemic, duration of drug use, the proportion of patients with long-term withdrawal during the epidemic, cravings, ACS, and PA. Correlation and multiple linear regression analysis showed that duration of drug use, ACS, and stable jobs were significant predictive factors for PA in patients with HUD, while long-term withdrawal, ACS, and stable jobs during the epidemic were significant predictive factors for PA in patients with MAUD.Conclusions: Our study demonstrated the factors for PA in patients with HUD and MAUD during the pandemic. The results provided a basis for the comprehensive understanding of the PA of patients with SUDs and the development of targeted treatments.

Adult-Attention Deficit Hyperactive Disorder Symptoms Seem Not to Influence the Outcome of an Enhanced Agonist Opioid Treatment: A 30-Year Follow-Up.

The role of opioids and opioid medications in ADHD symptoms is still largely understudied. We tested the hypothesis that, in Heroin Use Disorder (HUD), when patients are treated with Agonist Opioid medications (AOT), treatment outcome is associated with the presence of Adult Attention-Deficit/Hyperactive Disorder (A-ADHD) symptomatology. A retrospective cohort study of 130 HUD patients in Castelfranco Veneto, Italy, covering 30 years, was divided into two groups according to the Adult ADHD Self-Report Scale (ASRS) score and compared them using demographic, clinical and pharmacological factors. Survival in treatment was studied by utilizing the available data for leaving treatment and relapsing into addictive behavior and for mortality during treatment as poor primary outcomes. Thirty-five HUD subjects (26.9%) were unlikely to have A-ADHD symptomatology, and 95 (73.1%) were likely to have it. Only current age and co-substance use at treatment entry differed significantly between groups. Censored patients were 29 (82.9%) for HUD patients and 70 (73.9%) for A-ADHD/HUD patients (Mantel-Cox test = 0.66 p = 0.415). There were no significant linear trends indicative of a poorer outcome with the presence of A-ADHD after adjustment for demographic, clinical and pharmacological factors. Conclusions: ADHD symptomatology does not seem to exert any influence on the retention in AOT of HUD patients.

The ineffective emotion regulation strategies of heroin use disorder patients: An event-related potential study

BackgroundPeople with substance use disorders (SUDs) usually experience emotion dysregulation, which may be a consequence of or a risk factor for the development and maintenance of substance misuse. Despite growing evidence on emotion dysregulation among people with SUDs, relatively few studies have explored emotion dysregulation in heroin use disorder (HUD) patients. MethodsUsing event-related potentials (ERP), we compared the emotion regulation ability of 33 HUD patients and 30 healthy controls according to their average electroencephalogram amplitudes of the late positive potential (LPP) component in 400–1000 ms and 1000–2000 ms time windows, while viewing neutral and unpleasant emotional pictures, and using emotion regulation strategies (expressive suppression, cognitive reappraisal, and a combination) while viewing unpleasant pictures. We recorded their mood states and how successfully they used emotion regulation strategies in each block using 7-point scales. ResultsRelative to healthy controls, the LPP amplitudes of HUD patients were significantly lower when viewing emotional stimuli (pearlyLPP < 0.05) and using emotion regulation strategies (all p < 0.05). The left hemisphere was more active in healthy controls (pearlyLPP < 0.05, plateLPP < 0.01); there were no differences in scalp position activation among HUD patients. DiscussionCompared to healthy controls, HUD patients’ emotional arousal and emotion regulation ability were impaired, as reflected by the LPP component. Their abnormal scalp activation pattern may imply abnormal brain activity. Future research could explore this with electroencephalogram source analysis techniques, functional magnetic resonance imaging, or other technologies. Intervention effects for emotion dysregulation in HUD treatment are also worth exploring.

Differences in cue-induced brain activation between long-term methadone maintenance treatment and protracted abstinence in heroin use disorder patients: a functional magnetic resonance imaging study.

Heroin use disorder (HUD) remains one of the gravest public health issues in China. Methadone maintenance treatment (MMT) and protracted abstinence (PA) are the most commonly used treatments for HUD. Although both treatment approaches can alleviate heroin cravings, a previous study found that MMT patients had stronger cue-induced brain activation than patients undergoing PA; however, the changes associated with long-term treatment are unclear. Male patients with HUD who had been undergoing either PA (n=24) or MTT (n=21) for approximately 12 months, together with 20 demographically matched healthy controls, completed an event-related functional magnetic resonance imaging (fMRI) task. The subjective craving for heroin was evaluated using a visual analog scale. Compared to the healthy controls, the MMT and PA groups demonstrated significantly higher brain activation in the left pallidum, middle occipital gyrus, postcentral gyrus, anterior cingulate cortex, middle cingulate cortex, inferior parietal lobule, superior parietal lobule, amygdala, hippocampus, right inferior temporal gyrus, inferior frontal gyrus triangularis, and caudate during exposure to heroin-related cues. Compared to those undergoing PA, patients in the MMT group demonstrated significantly higher brain activation in all of these regions. Except for the left inferior parietal lobule and left superior parietal lobule, there were no statistically significant differences between the PA and healthy control groups. The MMT patients showed significantly higher subjective cravings before and after exposure to heroin cues than the PA group, but there was no significant difference in the change in subjective cravings between the 2 groups. The results suggested that although the HUD patients receiving long-term MMT complied with the treatment, they still had higher subjective cravings and cue-induced brain activation than those undergoing PA. Therefore, long-term PA appears to be more beneficial than MMT in reducing the salience value of drug cues in patients with HUD.

Differences in the amplitude of low-frequency fluctuation between methamphetamine and heroin use disorder individuals: A resting-state fMRI study.

IntroductionMethamphetamine has surpassed heroin as the most popular abused drug in China. Although the use of both heroin and methamphetamine leads to use disorders through dysfunction of the dopamine pathway, the incidence of psychiatric disorder caused by methamphetamine abuse is higher than the incidence of psychiatric disorder caused by heroin abuse. The difference in resting‐state function between heroin use disorder (HUD) and methamphetamine use disorder (MAUD) and the relationship between resting‐state function and psychiatric disorder related to MAUD are unknown.MethodsIn the present study, 21 male individuals with MAUD, 21 demographically matched individuals with HUD, and 21 normal controls (NC) were recruited. The amplitude of low‐frequency fluctuation (ALFF) during resting‐state brain function was measured by magnetic resonance imaging. Psychiatric status was evaluated by the Symptom Checklist‐90 (SCL90).ResultsIndividuals with MAUD had increased SCL90 scores compared to those of the NC for anxiety, paranoia, and additional items, and the hostility score was significantly increased compared to that of individuals with HUD. There is no significant difference between HUD and NC individuals. Individuals with MAUD had increased ALFF compared to those of the NC for thalamus, right postcentral, and right inferior temporal gyri, but a decreased ALFF in the cerebellum. Individuals with HUD had significantly increased ALFF compared to those of the NC for left middle frontal gyrus but a decreased ALFF in the left postcentral gyrus. Individuals with MAUD had significantly increased ALFF compared to those of the HUD for thalamus, the right inferior temporal, and bilateral postcentral gyri, and the ALFF of cerebellum and left middle frontal was significantly increased.ConclusionsMethamphetamine can induce more serious psychiatric disorders than heroin. The resting‐state function involved in mood adjustment, the auditory, and memory‐related brain regions may affect psychotic symptoms related to MAUD.

The Conceptual Framework of Dual Disorders and Its Flaws.

When psychiatric illness and substance use disorder coexist, the clinical approach to the patient is, unsurprisingly, awkward. This fact is due to a cultural context and, more directly, to the patient’s psychiatric condition and addiction behaviors—a situation that does not favor a scientific approach. In dual disorder facilities, several types of professionals work together: counselors, social workers, psychologists, and psychiatrists. Treatment approaches vary from one service to another and even within the same service. It is crucial to provide dual disorder patients with multiple treatments, comprising hospitalization, rehabilitative and residential programs, case management, and counselling. Still, when treating dual disorder (DD) heroin use disorder (HUD) patients, it is advisable to follow a hierarchical algorithm. First, we must deal with addiction: by detoxification, whenever possible. This means starting most patients on anti-craving pharmacological maintenance, though aversion therapy may be appropriate for a few of them. Opiate antagonists may be used with heroin-addicted patients as long as those patients are only mildly ill. In contrast, agonist opioid medications, i.e., buprenorphine and methadone suit moderately and severely ill patients, respectively. Achieving control of mood instability or psychotic episodes is the next step, to be followed by a prevention strategy to counteract residual cravings and dominate mood disorders or psychotic episodes through long-term pharmacological maintenance that is focused on a double target.

Can the migration process influence the clinical expression of heroin use disorder in migrants to Italy?

For some time now, there has been a strong consensus that the migration process can influence the onset, course, development, outcome, and clinical aspects of psychiatric pathologies. In this study, we have analyzed the influence of the migration process on the clinical expression of heroin use disorder (HUD). In a naturalistic case-control study, we compared, both at univariate and multivariate level, 30 migrant HUD (M-HUD) patients with 30 age/gender-matched Italian HUD (IT-HUD) patients. We also analyzed demographic data, drug addiction history, psychopathological symptoms, addictive behavior, and emotional reactivity to life events. Compared with IT-HUD pairs, at HUD Agonist Opioid Treatment, M-HUD patients were characterized by inadequate income and the presence of legal problems. They were more frequently at stage 3 of heroin addiction, with a concomitantly less frequent use of stimulants. Their age at the onset of heroin use was greater than that of subjects in the IT-HUD group. HUD post-traumatic stress disorder spectrum was present and was more severe in all M-HUD patients, but grief reactions and maladaptive behavior were the most discriminant traits. No differences were found in terms of addictive behaviors related to heroin craving or with respect to the severity/typology of psychopathology specific to HUD. The migratory process does not seem to be correlated with addictive behaviors or with psychopathology specific to HUD. It partly affects HUD history, and specifically correlates with emotional reactivity to loss and traumatic life events, so suggesting that in M-HUD individuals, the link between the migratory syndrome and HUD is very close.

κ Opioid Receptor 1 Single Nucleotide Polymorphisms were Associated with the Methadone Dosage.

Background: Heroin use disorder (HUD) is a complex brain disease that includes multiple phenotypes. Heroin acts primarily as a mu-opioid receptor (OPRM1) agonist. The κ opioid receptor 1 (OPRK1) is critically involved in abstinence and remission. Multiple studies confirm that the OPRM1 and OPRK1 genes are associated with HUD. However, their relationship with the addictive phenotype is still unclear. This study was designed to identify the genetic polymorphisms within OPRM1 and OPRK1 with six HUD phenotypes. Methods: A total of 801 patients with HUD were recruited from the Methadone Maintenance Treatment Program in Xi'an. We identified eight potential functional single nucleotide polymorphisms (SNPs) in the two genes that were genotyped using SNaPshot SNP technology. We then performed a case-control association analysis, investigated particular disease phenotypes, and assessed the extent of epistasis among the variants of the two genes. Results: The OPRK1 rs3802279, rs3802281, and rs963549 genotypes were significantly associated with methadone dosage analyzed by Pearson's chi-square test or binary logistic regression to correct for covariates. The rs3802279 CC, rs3802281 TT, and rs963549 CC genotype carriers required a lower methadone maintenance dose per day. Multifactor dimensionality reduction analysis indicated strong interactions between sex and OPRK1 rs963549. The results of the OPRM1 genotyping did not reveal any associations with the various HUD phenotypes. Conclusion: These findings support an important role of the OPRK1 polymorphism in determining the daily methadone dose and may guide future studies in identifying additional genetic risk factors for HUD.

Specific personality traits and associated psychosocial distresses among individuals with heroin or methamphetamine use disorder in Taiwan

Previous studies showed the association between substance use disorders (SUDs) and borderline and antisocial personality disorders. Substance abusers may have emotional, somatic and interpersonal distresses. This study aimed to investigate the associations between substance, personality and psychosocial distresses. This cross-sectional, questionnaire-based study recruited 39 individuals with heroin use disorder (HUD), 111 with methamphetamine use disorder (MUD) and 101 as the control group in a rural area of Taiwan. The Tridimensional Personality Questionnaire (TPQ) and Opiate Treatment Index were used to assess the association between personality and psychosocial conditions. Deviations of the three personality dimensions of TPQ (novelty seeking, harm avoidance, and reward dependence) could reflect eight personality patterns. We found SUD was associated with high novelty seeking and harm avoidance traits and explosive (borderline) personality pattern, whereas HUD was also linked with sensitive (narcissistic) pattern. Subjects with HUD tended to have more deviant personality traits than subjects with MUD. For subjects with SUDs, all three personality dimensions and sensitive (narcissistic) personality patterns were associated with emotional and somatic distresses, and those with explosive (borderline) and sensitive (narcissistic) patterns had poor social functioning. Our results indicate substance abusers with high novelty seeking and harm avoidance, corresponding to explosive (borderline) or sensitive (narcissistic) patterns, to have a higher tendency to suffer from somatic and psychosocial distresses.